1. Field of the Invention
The present invention is in the field of methodology and materials for performing autologous tissue transplants. More particularly, the present invention is directed to a solution suitable for treating autologous tissue after the tissue has been removed from a mammal, to render the tissue more suitable for handling and molding it into the desired shape and obtain predictable results after implantation in the mammal.
2. Brief Description of the Prior Art
Significant advances have been made in the field of treatment of defective heart valves due to abnormalities during fetal development, or due to infectious or degenerative diseases. These surgical treatments most often require the use of biocompatible materials that can be either synthetic polymers or of biological origin, either from the patient (autologous), an individual of the same species (homologous), or different species (heterologous or xenograft). Defective heart valves are replaced with mechanical valves or tissue valves, such as cadaver or animal aortic valves (bioprosthesis). Because of their more-or-less predictable mechanical wear properties, the mechanical prostheses have been proven suitable for their intended purpose, primarily in younger patients. However, mechanical prostheses have their disadvantages because patients having them require long-term, constant and vigorous anti-coagulant therapy. In older patients however the bioprostheses have been favored mainly because they do not require anti-coagulation therapy, and in older patients they do not tend to undergo calcification as often as they tend to do in younger patients. Cryo-preserved homografts have been used widely in the western world during the recent years. However, these are hard and expensive to obtain, ship and store, and their availability on a world-wide basis appears to be limited.
As is known, heart valve repair or replacement and many other implant operations require soft connective tissue which in preparation for implantation needs to be sized and cut into specific shapes. A substitute for such soft connective tissue of biological origin can be provided by flat sheets of certain synthetic materials. However, it is difficult to find synthetic materials which can match the compliance of the native tissue they are intended to replace, and which do not engender adverse reaction by the recipient of the implant. Autologous tissues, such as pericardium, hold the promise for an ideal soft tissue replacement material in implants, and fresh autologous pericardium has been used in the prior art as a tissue source for repairing a variety of heart lesions, including heart valves. However, results with the use of such fresh untreated autologous tissue were less than satisfactory because tissue contraction distorted the repair, and in case of heart valves, tended to render the leaflets non-functional some time after operation. Generally speaking, the problem with fresh autologous soft connective tissue, such as pericardium, is that such tissues are often too soft and flexible to cut and otherwise handle especially during open heart surgery where an atmosphere of urgency prevails. As an improvement Dr. Duran (one of the inventors of the present invention) developed a procedure in which the autologous tissue that has been freshly obtained from the patient operated on, is treated with 0.5% glutaraldehyde in a mold for 10 minutes. Thereafter, it is cut into the desired shape dictated by the mold and is placed in the patient as new replacement heart valve leaflets. Although this procedure works reasonably well, the disadvantage of tissues treated by glutaraldehyde is that, similarly to xenografts, such tissues may well undergo calcification in long term implants.
The present invention provides an alternative to glutaraldehyde fixation of autologous tissues and yet eliminates the problems caused by contraction of fresh tissue and the difficulty of handling and manipulating soft tissue. Because the invention avoids the above-noted problems by treating the autologous tissue with an aqueous solution of alcohols and other materials, prior art describing solutions and methods for treating biological tissues and specimens are thought to be of interest as background to the present invention. Such prior art can be found in U.S. Pat. Nos. 5,558,875; 5,296,514; 5,276,006; 4,323,358 and 4,329,492. Among the foregoing, the most recently issued U.S. Pat. No. 5,558,875 describes a process of preparing a collagenous prosthesis by soaking tissue in an organic detergent for sufficient time to disrupt the cell membrane and to solubilize the cellular membrane proteins of the collagenous tissue and thereafter extracting and removing the cellular membrane proteins from the collagenous tissue by mechanical washing to obtain the prosthesis and thereafter preserving the prosthesis in alcohol. The process is said to preserve the elasticity of the prosthesis.
The following articles or scientific publications also provide background of interest to the present invention: Chachques et al., Ann. NY Acad Sci. 1988, 529:184; Love et al., J. Heart Valve Dis 1992: 1:232-41; Chauvaud et al., J. Thorac Cardiovasc Surg. 1991, 102:171-8; Duran et al., J. Thorac Cardiovasc Surg. 1995, 11-511-6; Vyavahare et al., 4th Scientific Meeting International Association for Cardiac Biological Implants, Washington D.C., May, 1997; Ritter et al., Plastic and Reconstructive Surgery. 101 (1): 142-6, January, 1998; and Vetter et al., J. Thorac Cardiovasc Surg, 35(1):11-5, February 1987.
It is an object of the present invention to provide a composition (solution) and method for treating autologous soft tissue so as to render it easier to handle and shape for implantation, while avoiding disadvantages caused by aldehyde treatment of such tissue.
It is another object of the present invention to provide a composition (solution) and method that meets the foregoing objective and which treats the autologous soft tissue during a surgical procedure and while said procedure is in progress.
The foregoing and other objects and advantages are attained by exposing for approximately 2 to 8 minutes a fresh autologous tissue, such as pericardium, to an aqueous solution containing approximately 10 to 70% by volume of a water-miscible non toxic polar solvent, such as ethyl alcohol, approximately 2 to 30% by weight of polyethylene glycol of a molecular weight between approximately 6,000 to 15,000 D, and approximately 0.01 to 1.0% by weight of heparin. The tissue preferably, and most frequently in accordance with the procedure is immersed in the above-described solution while placed in a suitable mold. In case of preparing the tissue for heart valve replacement the mold is configured to provide the appropriate shape and dimension for the replacement heart valve leaflets. The soft tissue implant treated in the foregoing manner temporarily becomes more rigid and easier to handle during surgical procedure than unprepared fresh tissue. However, within approximately the time taken to perform the surgical procedure of implantation the treated tissue regains its original physical properties, including its elasticity.